Prostate cancer imaging with positron emission tomography (PET) has been facilitated by the recent development of the radioactive tracer fluorine-18 fluorocholine (F-18 FCH). Like other substrates for the enzyme choline kinase, F-18 FCH demonstrates increased accumulation in malignant cells. In addition to whole-body cancer staging, F-18 FCH PET may potentially be applied to specifically image the prostate gland for guiding biopsy and optimizing local treatments such as brachytherapy. These applications can be realized through computer image registration with other diagnostic modalities, based on the hypothesis that F-18 FCH uptake in the prostate is higher in malignant areas. This phase I STTR project will test this hypothesis and assess the feasibility of the proposed application through the following aims: (1) preliminarily evaluate F-18 FCH PET for sextant localization of prostate cancer using step-section analysis of prostate specimens for correlation, (2) apply voxel, surface, and feature based methods of image registration to compare F-18 FCH PET images with histopathology and validate the hypothesized correlation, and (3) compare performance of various prostate biopsy protocols in individual subjects by computer simulation and determine the potential of F-18 FCH PET imaging for patient-specific selection of the optimal protocol. Completion of these aims with positive results will lead to a phase II proposal to develop multi-modality image registration for a PET-guided approach to prostate biopsy and treatment. Guided biopsy may lead to a reduction in false negative biopsy results and their associated complications. These technologies may also be applied for optimizing local therapy and measuring therapeutic response in prostate and other types of cancer.